Epidemiology and socioeconomic correlates of brain and central nervous system cancers in Asia in 2020 and their projection to 2040

Brain and central nervous system (CNS) cancers constitute a heterogeneous group of cancers with poor 5-year survival rates. We aimed to report the epidemiology of brain and CNS cancers in Asia in 2020 and their projections up to 2040 by age, sex, and country, as well as their correlation with socioeconomic status. We extracted data from the 2020 Global Cancer Observatory (GLOBOCAN). Numbers, age-standardized incidence rates (ASIRs) and mortality rates (ASMRs), 5-year prevalent cases and rates, mortality-to-incidence ratios (MIRs), and crude rates were calculated. The human development index (HDI) and current healthcare expenditure (CHE)-to-gross domestic product (GDP) ratio were included as indicators of socioeconomic status. Additionally, the numbers of new cases and deaths were predicted from 2025 to 2040 by multiplying the anticipated population during this period by age-standardized rates. In 2020, there were 166,925 new cases of brain and CNS cancers in Asia, indicating a 5-year prevalence rate of 9.40 per 100,000. We also estimated the total ASIR, ASMR, and MIR as 3.20, 2.60, and 0.83, respectively. There were significant negative correlations between HDI and MIR (correlation coefficient: − 0.538, p value < 0.001) and significant positive correlations between CHE/GDP% and ASIR (correlation coefficient: 0.388, p value: 0.010) and ASMR (correlation coefficient: 0.373, p value: 0.014). In 2040, there will be 232,000 new cases of brain and CNS cancers and 200,000 subsequent deaths in Asia. Our study revealed higher brain and CNS cancer rates in Western Asia among males and elderly individuals. These findings can aid policymakers in enhancing cancer care and suggest the consideration of risk factors in future research. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-73277-z.


Study variables
The incidence and mortality rates of brain and CNS cancers were collected, followed by the calculation of MIRs by dividing the crude mortality rate by the incidence rate.MIR, which represents the quality of care in the healthcare setting, has lower values when screening and overall cancer management care are superior to other equally derived MIRs in our study 14 .In addition, to report the progression and mortality risk of brain and CNS cancers in individuals under the age of 75 years, we noted the incidence and mortality cumulative risk percentages.A further indicator in our study was CHE/GDP%, which represents the financial allocation to healthcare in a country and signifies the pivotal contribution of healthcare to the total economy.
The HDI was incorporated to consider the socioeconomic level of a country.It is a universally used composite index of life expectancy, mean education acquired by 25-year-old and older individuals, the predicted duration of school-aged children's education, and per capita income indicators 15 .
Briefly, the data in our study were categorized by age, sex, region (North America, Latin America and the Caribbean, Europe, Africa, and Oceania) Asian subregion (Western [Turkey, Iraq, Israel, Azerbaijan, Syrian Arab Republic, Yemen, Saudi Arabia, Georgia, Jordan, Armenia, Lebanon, Gaza Strip and West Bank, United Arab Emirates, Oman, Bahrain, Kuwait, and Qatar], South Central [India, Iran, Pakistan, Uzbekistan, Bangladesh, Kazakhstan, Afghanistan, Sri Lanka, Kyrgyzstan, Turkmenistan, Tajikistan, Nepal, and Bhutan], Eastern [China, Japan, Republic of Korea, Democratic Republic of Korea, and Mongolia], and Southeastern Asia [Indonesia, Viet Nam, Thailand, Philippines, Myanmar, Malaysia, Cambodia, Singapore, Lao People's Democratic Republic, Brunei Darussalam, and Timor-Leste]), and Asian country.

Statistical analysis
The average total rates from adjacent countries were used to calculate all national age-and sex-adjusted incidence rates of cancer.We then calculated the 5-year incidence of brain and CNS cancers by using the ratio of incidence to five-year incidence (adjusted by age, sex, and country) of the Nordic regions from 2006 to 2015, as illustrated below: To estimate the rates, we extracted the 2020 population data from the World Population Prospects of the United Nations, which were projected and last revised in 2019.Additionally, we extracted HDI data from the Human Development Report Office of the United Nations Development Programme 15 .The Global Health Observatory data repository of the WHO was used to extract data on CHE as a proportion of GDP in 2019 16 .The design of our study and the results are in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting 17 and the Strengthening the Reporting of Observational Studies in Epidemiology statements 18 .
The figures and tables in our study provide the incidence and mortality cases, crude incidence and mortality rates, prevalent cases and rates of 5-year prevalence, ASMRs, and ASIRs.All rates were considered to be expressed in 100,000 people.Standardization was performed directly according to the 1966 Segi-Doll World standard population.Age groups were stratified with intervals of 10 or five years.Furthermore, the bivariate correlation test analyzed the associations between ASIRs, ASMRs, and MIRs of brain and CNS cancers with the CHE/GDP% and HDI of the countries with existing data.Pearson's correlation coefficient was employed, and the results were stratified into three categories: weak (< 0.3), moderate (0.3-0.5), and strong (> 0.5) correlations.A statistically significant p value was considered < 0.05 in a two-sided test.The number of new cases and deaths from 2025 to 2040 were predicted through the multiplication of the anticipated population by the 2020 ASIRs and ASMRs.The 95% uncertainty intervals (UIs) for the estimated number of new cancer cases and cancer deaths, broken down by sex and site for all ages, were calculated using the standard error of the crude incidence or mortality rates used in the estimation.The cumulative risk percentages were calculated by determining the likelihood that an individual would develop or die from brain and CNS cancers before the age of 75.This was done using the age-specific incidence and mortality rates collected for each population group.The cumulative risk was computed by summing the age-specific rates across all age intervals up to 75 years and then applying standard life table methods to estimate the cumulative probability of cancer incidence or mortality within that age range.Version 4.3.2 of R statistical software was used for statistical analysis 19 .

Prevalence, incidence, mortality, and MIR in the globe and Asia in both sexes
Worldwide, there were 837,152 cases of brain and CNS cancers diagnosed within the previous five years in 2020, with a 5-year prevalence rate of 10.70 per 100,000.Moreover, there were 308,102 estimated new cases of brain and CNS cancers in 2020 (95% UI: 295,692.0-321,033.0),indicating a crude rate of 4.00 per 100,000, an ASIR value of 3.50 per 100,000, and a cumulative risk of 0.61%.In 2020, brain and CNS cancers led to 251,329 estimated deaths worldwide (95% UI: 244,434.0-258,418.0),representing a crude rate of 3.20 per 100,000, an ASMR of 2.80 per 100,000, and a cumulative risk of 0.54%.Accordingly, we measured the MIR of brain and CNS cancers equal to 0.80 globally (Table 1).
In Asia, the estimated 5-year prevalence rate of brain and CNS cancers was 9.40 per 100,000, indicating a total of 435,532 cases.Additionally, 166,925 new cases were estimated of brain and CNS cancers (95% UI: 159,699.0-174,478.0),representing a crude rate of 3.60 per 100,000, an ASIR value of 3.20 per 100,000, and a cumulative risk of 0.52%.These cancers led to 137,646 estimated deaths in Asia in 2020 (95% UI: 131,171.0-144,440.0),resulting in a crude rate of 3.00 per 100,000, an ASMR of 2.60 per 100,000, and a cumulative risk of 0.47%.The MIR of these cancers was 0.83 in Asia (Table 1).

Age patterns
The 70 + age group accounted for the highest crude incidence rate (12.70 per 100,000) and crude mortality rate (12.20 per 100,000) in both sexes in Asia (Table 3).In terms of MIR, this age group also presented the highest MIR, 0.96.Moreover, people within the age range of 10-19 years presented the lowest crude incidence rate (1.00 per 100,000) and crude mortality rate (0.60 per 100,000).The lowest MIR belonged to the 0-9 age group (0.53).There were minimal variations in the incidence (Fig. 2A) and mortality rates (Fig. 2B) of brain and CNS cancers until the age of 40-49, after which there was a substantial increase in both incidence and mortality rates.The number of incident cases decreased up to the 15-19 year age group, then increased to the 55-59 year age group, and peaked in the 70 + year age group (Fig. 2A).Deaths generally exhibited an increasing trend with advancing age (Fig. 2B).

Men
In 2020, the estimated 5-year prevalence rate was 9.40 per 100,000 men in Asia.Our study also highlighted a total of 91,992 new male cases were estimated of brain and CNS cancers (95% UI: 86,579.5-97,742.8),representing a crude rate of 3.90 per 100,000, an ASIR of 3.50 per 100,000, and a cumulative risk of 0.59%.With respect to the mortality of Asian men, brain and CNS cancers resulted in 76,169 estimated deaths in 2020 (95% UI: 71,192.7-81,493.1).The crude mortality rate was estimated 3.20 per 100,000, with an ASMR of 2.90 per 100,000 and a cumulative risk of 0.53%.We measured the MIR of brain and CNS cancers as 0.82 in men in Asia (Table 1).Similar to the total population, the 70 + year age group presented the highest crude rates of incidence (14.50) and mortality (13.90) in men (Table 3).

Women
Among women, the estimated 5-year prevalence rate of these cancers was 9.40 per 100,000.In this regard, 74,933 new cases were estimated of brain and CNS cancers (95% UI: 70,236.4-79,943.6).The crude incidence rate among women was 3.30 per 100,000, the ASIR was 2.80 per 100,000, and the cumulative risk was 0.46%.Brain and CNS cancers also led to 61,477 deaths among Asian women in 2020 (95% UI: 57,294.0-65,965.4),with a crude mortality rate of 2.70 per 100,000, an ASMR of 2.30 per 100,000, and a cumulative risk of 0.41%.The MIR of brain and CNS cancers was 0.82 in women, which was the same as that in men (Table 1).Moreover, compared with the total population and men, the 70 + age group presented the highest crude rates of incidence (11.10) and mortality (10.80) among the other age groups (Table 3).

Projections to 2040
We estimated that the number of newly diagnosed cases of brain and CNS cancers in Asia will increase by 39.30%, from 166,925 in 2020 to 232,000 cases in 2040 (Fig. 5A).Similarly, deaths caused by brain and CNS cancers are estimated to increase by 45.00%, from 137,646 in 2020 to 200,000 deaths in 2040 (Fig. 5B).There is a need for annual decreases of more than 1.60% in incidence and 1.80% in mortality in Asia to ensure that there would be fewer brain and CNS cancer cases in 2040 than in 2020.

Discussion
In the present article, we provided an update on the epidemiology of brain and CNS cancer in Asia via the GLOBOCAN 2020 estimates.There were five main results in our study.First, we presented the prevalence, incidence, and mortality-related metrics of brain and CNS cancers in Asia, which are lower than those estimated worldwide.Second, we found that the countries with the highest ASIRs and ASMRs, namely, Armenia, Turkey, Iran, and Georgia, are all located in Western Asia and South Central Asia.Third, we revealed the age and sex patterns of these cancers, with the highest rates occurring in males and 70 + years.Fourth, we presented significant correlations of the assessed epidemiological metrics with the HDI and CHE/GDP%.Finally, we discussed the estimated projections of brain and CNS cancers that are expected to increase by approximately 40% until 2040.
In general, our estimates were consistent with trends in incidence and mortality reported in previous GBD studies, which evaluated the burden from 1990 to 2019 2,4 .Our ASIR estimates were slightly lower than those of GBD, possibly due to differences in data sources, estimation methods, and time periods 20 .Longitudinal analysis of the burden of brain and CNS cancers has similarly revealed increasing trends in the ASIR and decreasing trends in the ASMR across Asia and the globe 2,4 .Moreover, the GBD estimates from 1990 to 2019 revealed that West Asia always had the highest ASIRs, which aligns with our estimates in 2020.The ASIR was 6.01 among both sexes in Western Asia in 2019 in the GBD study, whereas it was 5.00 in Western Asia in 2020 in our study 4 .However, the highest levels of ASMRs were reported in Central Asia from 2005 until 2019 4 , which is not compatible with our findings, as we have shown that Western Asia still holds records of ASMRs in 2020.This might be explained by the fact that we used real data, whereas the GBD study uses estimation models.We also reported the values in 2020, while the GBD study used the data up to 2019.
As expected, the incidence and mortality of brain and CNS cancers exhibited an upward age trend, peaking after 40-49 years of age and maximizing in elderly individuals over 70 years of age.Similarly, the total glioma incidence increases with age, with a peak at 50-59 years of age 21 .Sex has also been shown to have a significant effect, with men being more likely to develop brain or CNS cancers in all age groups, possibly due to genetics and lifestyle factors 22 .This evidence highlights the role of age and sex as critical risk factors for brain and CNS cancers.
In this study, we revealed significant positive correlations between CHE/GDP% and both the ASIR and the ASMR alongside significant negative correlations between the HDI and MIR findings of brain and CNS cancers.As previously explained, CHE/GDP indicates the proportion of resources allocated to health care, and the HDI is a composite indicator of socioeconomic status 23 .Well-developed countries with higher HDIs possess more efficient healthcare systems that help with better surveillance and management of cancers 24 .Moreover, in these countries, better access to advanced medical treatments also affects the prognosis of patients 24 .One reason for the positive correlation between the ASMR and CHE/GDP% could be that, with better diagnosis, a larger proportion of overall mortality is attributed to brain and CNS cancers.A previous GLOBOCAN study has even shown that countries with different levels of HDI have distinct profiles of cancer incidence and mortality 25 .These findings suggest that countries with different socioeconomic statuses need tailored public health approaches to better manage brain and CNS cancers.Various diagnostic techniques and practices, unspecific genetic and environmental risk factors, and even races and ethnicities can account for such massive geographical and regional variation in the incidence and mortality of CNS cancer 26,27 .For example, countries with higher socioeconomic status have better technological capacity to correctly diagnose brain tumors, which may account for some of the variation.We used an approach that assumes an inverse linear relationship between the prevalence-to-incidence ratio and the HDI.This assumption is based on the understanding that regions with higher HDI typically have better healthcare systems, leading to earlier detection, more effective treatment, and thus higher survival rates, which result in a higher prevalence of survivors.This relationship has been observed in previous studies and  provides a logical basis for our estimation method.However, we recognize that this assumption introduces potential limitations, as it may not account for all regional healthcare variations or other factors influencing cancer survival.Therefore, while this assumption is reasonable and supported by existing evidence, it requires careful consideration when interpreting the results.We also forecasted an increasing trend in the incidence and mortality of brain and CNS cancers until 2040.Population aging is occurring more rapidly in Asia than in Western countries, and the number of Asian people older than 65 is estimated to increase to 857 million in 2050 28 .More efficient healthcare systems are needed to prevent, diagnose, and manage brain and CNS cancers.Apart from unchangeable risk factors (age, sex, and genetics), the only established modifiable factor increasing the risk of brain and CNS cancers is ionizing radiation 29 .More causal studies are needed to identify and assess numerous environmental risk factors to help better policies for cancer prevention.Enriched healthcare systems can also improve patient prognosis and reduce mortality 30 .However, one must note that enhanced hospital technologies and accessible professionals in developing countries might lead to higher incidence rates, which do not necessarily indicate a poorer healthrelated profile.
Our study has several limitations.First, there is a lack of epidemiological data on histopathological types of brain and CNS cancers.Different types of cancers exhibit considerable heterogeneity in terms of sex, age, race, and prognosis profiles.Second, low-and middle-income countries might have had less reliable data, leading to considerable uncertainties in estimates.Moreover, relevant data on brain and CNS cancer risk factors were not included in the database, and we could not explore the risk factors that contributed to the mortality of affected people.Additionally, the projections were calculated solely by assuming changes in the world population size and age structure, and we did not account for possible changes in age-specific incidence, globally or within countries.The projected incidence and mortality rates also do not take into account improvements in diagnostics or treatments.Third, one significant limitation in the epidemiology of CNS cancers is the challenge in identifying and collecting data on benign tumors.The ICD codes C70-C72 primarily cover malignant neoplasms, and while some cancer registries can identify and record benign tumors (D42-D44), others may either fail to collect this data or misclassify benign tumors as malignant.This inconsistency introduces bias, particularly in incidence and prevalence estimates, although it has a lesser impact on mortality rates.Also, the tumors of the pituitary or  pineal glands were not included in this report, and can be considered in other studies.Fourth, in regions where national cancer registry data were incomplete or unavailable, we used the average incidence and mortality rates from adjacent countries to estimate figures for those countries.This approach was necessary to provide more comprehensive epidemiological data, but it may introduce some degree of bias or inaccuracy.

Conclusions
Brain and CNS cancers remain major public health concerns in Asia.In our study, we presented the prevalence, incidence, mortality, and MIR according to sex, age, country, and Asian subregion.Moreover, we presented possible correlates with socioeconomics and estimated the epidemiological burden of these cancers in 2020.
Overall, Western Asian, male, and elderly individuals had higher incidence rates and mortality rates.The findings of our study can help policymakers have a better perspective on the profile of brain and CNS cancers and enhance healthcare systems regarding the prevention, diagnosis, and management of these cancers.The burden attributable to each risk factor should be considered in future studies.Due to the unlikelihood of stable incidence rates, alternative scenarios are provided.

Fig. 1 .
Fig. 1.Distribution of (A) five-year prevalence rate, (B) age-standardized incidence and (C) age-standardized mortality rates per 100,000 of brain and central nervous system cancers among both sexes in Asia in 2020.

Fig. 2 .
Fig. 2. (A) Incident numbers and incidence rate, and (B) mortality numbers and mortality rate of brain and central nervous system cancers among males and females in each age group in Asia in 2020.The column bars represent the numbers of incident cases and deaths related to the left y-axis.The lines represent the incidence and mortality rates related to the right y-axis.

Fig. 3 .
Fig. 3. (A) Five-year prevalence rate, (B) age-standardized incidence and (C) age-standardized mortality rates per 100,000 of brain and central nervous system cancers in Asia in 2020, by country and sex.

Fig. 5 .
Fig.5.Estimated brain and central nervous system cancers (A) incidence and (B) mortality from 2020 to 2040.The baseline scenario (represented by the black line), posits that there are no alterations in incidence and mortality, meaning that any rise in numbers is solely attributed to changes in population size and composition.Due to the unlikelihood of stable incidence rates, alternative scenarios are provided.

Table 1 .
Five-year prevalence, incidence, and mortality metrics in 2020 of brain and central nervous system cancers for different geographic location in both sexes, males, and females.ASIR age-standardized incidence rate, ASMR age-standardized mortality rate, MIR mortality-to-incidence ratio.Rates are presented per 100,000 population.

Table 2 .
Five-year prevalence, incidence, and mortality metrics in 2020 of brain and central nervous system cancers for Asian countries in both sexes.ASIR age-standardized incidence rate, ASMR: age-standardized mortality rate, MIR mortality-to-incidence ratio.Rates are presented per 100,000 population.

Table 3 .
Incidence, mortality, and mortality-to-incidence ratio metrics of brain and central nervous system cancers in Asia in 2020 for different age groups among both sexes, males, and females.MIR mortality-toincidence ratio.Rates are presented per 100,000 population.